1. Field of the Invention
The present invention relates to opioid receptor agonist compounds and their use in the treatment of acute and/or chronic pain.
2. Background of the Invention
The study of compounds exerting their actions via the opioid receptor system has continued for nearly eight decades.1 Though this has been a broad effort, the fundamental driving force for this endeavor relates to the elimination or reduction of the side-effect profile produced by the most frequently used or abused opiates morphine (1) and heroin (2). The wealth of knowledge accumulated in this time is enormous and includes examples of milestone discoveries commensurate with its breadth from the original concept of an opiate receptor2 to the more recent cloning of three individual opioid receptor subtypes, mu3-5 delta6,7 and kappa.8-10 Belonging to the superfamily of G protein-coupled receptors (GPCR), postulated to possess seven helical transmembrane (7TM) spanning regions, they are now known to be anatomically distributed in both the central and peripheral nervous systems and aside from modulation of pain are intimately involved in a diversity of biological events ranging from of the modulation of immune response11 to hibernation.12 
Over 100 million patients experience acute or chronic pain annually in the United States caused by headache, muscle strains and sprains, arthritis, trauma, cancer, surgery, and back injuries, among others. Because pain impairs one's ability to carry out a productive life, pain in general and chronic pain in particular are serious health and economic problems. Patients with advanced cancer pain, osteoarthritis, rheumatoid arthritis, or neuropathic pain frequently do not achieve adequate relief of pain with existing drugs owing to limited efficacy. Hence, there is a significant unmet medical need for safer orally-active and parenteral products for treating mild-moderate and moderate-severe pain. Market statistics show a continuing unmet medical need for safer, easier-to-use and more effective treatments for both acute and chronic pain.
U.S. Pat. No. 6,559,159 discloses a variety of N-substituted 4β-methyl-5-(3-hydroxyphenyl)morphans as opioid kappa receptor selective pure antagonists, and their use in a variety of end uses such as treatment of disease states that are ameliorated by binding of the kappa opioid receptor such as heroin or cocaine addictions, among other uses. (see also Thomas et al, J. Med. Chem., 2002, 45, 3524-3530).
With the recent removal from the US market of various COX1 and COX2 mechanism based pain medications, there is a great need for new medications for treatment of acute and/or chronic pain, operating by different pathways so as to avoid the negative side effects of the withdrawn drugs. One potential pathway for pain treatment may be with the use of agonists for the opioid receptors, thus mimicking the pain alleviating aspects of the opiates, without the negative side effects of such illegal substances.